Key words: antiphospholipid syndrome, trombosis, pathogenesis
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1 26. XI,. 4/2011,.,..,..,., -..,,. 2GPI. -,.,,., -,, -, -,,,,, IL-1, IL-2, IL-6, IL-8, IL-12, IL-10, TNF, INF-. :,, N. Stoilov, R. Rashkov and R. Stoilov. ANTIPHOSPHOLIPID SYNDROME HISTORICAL DATA, ETI- OLOGY AND PATHOGENESIS Summary. Antiphospholipid syndrome is an autoimmune disease characterized by circulating antibodies against different phospholipids and their co-protein factors. The base manifestation of antiphospholipid syndrome is thrombosis. This process involves the endothelial cells, monocytes, platelets, and complement. Endothelial cells and monocytes can be activated by antibodies against 2GPI. Many autoimmune diseases in rheumatologycal practice including. RA and SLE API are characterized by accelerated atherosclerosis and therefore an increased risk of cardiovascular disease and mortality. As an immune-mediated process macrophages are included in its pathogenesis, which are transformed into foam cells, T cells, autoantibodies, autoantigens, which are usually components of the vessel wall, cholesterol particles and cytokines secreted by the cells presented in atherosclerotic plaques such as IL-1, IL-2, IL-6, IL-8, IL-12, IL-10, TNF, INF and platelet growth factor. Key words: antiphospholipid syndrome, trombosis, pathogenesis -, /, -. ( - ) [20] , - [2] ,, - VDRL (veneral disease research laboratory) [30]. -, VDRL,., [21] , -, - -., - [7]. - -, -, [22] ,,,
2 27,. IX,. 4/2011 [12]. -, (acl). - apl VDRL - [13].. - -,,, [16-18] ,. [44]. -, :, /, -, -. -, -, -. -.,.., 0,5% [9]. - -, 36% [44] : - (5%), Sjögren (2,2%), (1,8%). -,., 0,5%. - -,, - 12% : 1 : 3,5 1 : 7 [9] ,7., 1 17,9. : - 1 : , [33]. 1% ( ) - (CAPS). 50% - CAPS. -, - :, -,,,,,, HIV, HCV,. apl :,,, / -,. -, 1% 3% -,. -, -, GP I V S -
3 28. XI,. 4/2011.,.. XII C4b (acl). IgG, IgM, IgA, -. -, - IgG IgM, IgA., - -, - - 2GPI,, - V, S. -2- I,. 2GPI - -, acl, - - [1]. S. -., - S, Va VIIIa. -.,,. - [9]. - - :,, -,, [30-34].,, [4, 48]. -,, - [31]. -., -, 20%,,,,,., 10-20% -, /,,. - 10% :,,, - /, amaurosis fugax ( ),,,, -. -, - 1%: -, - Budd-Chiari. - apl.,.,,. -., apl 2GPI,, -, 2GPI.,, -, - -. apl -,,,, apl. -,,.. HLA. DR53, DR4, DQ7 DR5. - DR7 [23, 33, 34]., - 2GPI HLA
4 29,. IX,. 4/2011 DQB1*0604/5/6/7/9-DQA1*0102-DRB1 *1302 DQB1*0303-DQA1*0201-DRB1*0701 [5, 14]. - - HLA [15]. e,. - - acl - [9, 10, 24, 26, 39, 41, 46, 50]. Goel,, e, [37].,. V, - -,, 4G/5G MTHFR [25, 42, 44]. MTHFR ( ) , -,, -. [19, 35, 38, 45, 47]. -.,,. 2GPI , 1,. -, -. -, - 2-3b.,,, [28, 29, 40, 49]. -,, -..,.,,. - [49]., -, -.. 5,.. 2GPI [49] , [11]. -. [36]. -., -, (, ).,.,,. -,,., ù,, -,, -, -,,, - IL-1, IL-2, IL-6, IL-8, IL-12, IL-10, TNF, INF LDL, ( ), -, -. -
5 30. XI,. 4/2011.,.. LDL -, , 1 - (Th1).,. -. apl - 2GPI, GPI, CD4+T., 2GPI, , apl, ,. - -,., ,. -,.., apl. apl. -, amaurosi fugax. - :,, Guillain- Barre, apl. 35% 75% , -. -,, acl,.., -,.,,,, apl -. apl..,.,. - -
6 31,. IX,. 4/ %.,, ( 50%). -., ,,. -,,, -., , %, ,. Galli - IIb/IIIa Ib/IX 40% apl -, , -.,. -,. 1% -,. 15% GPI. -2-, -, -..,, apl,, - apl., -,. - HELLP (, -, ). 1., I.., W a s s e r m a n, A, A Neisser et C. Bruck. Eine serodiagnosticsche reaktion bei syphilis. Dtsch. Med. Wochenschr., 32, 1906,
7 32. XI,. 4/2011.,.. 3. A v c i n, T. et al. Pediatric antiphospholipid syndrome: clinical and immunologic features of 121 patients in an international registry. Pediatrics, 122, 2008, e A m i g o, M. C. et al. Renal involvement in primary antiphospholipid syndrome. J. Rheumatol., 9, 1992, C a l i z, A. R. et al. Lanchbury and G. R. V. Hughes. HLA class II gene polymorphisms in antiphospholipid syndrome: haplotype analysis in 83 caucasoid patients. Rheumatology, 40, 2001, M o n t a r u l i, B. et al. Factor V Arg506-->Gln mutation in patients with antiphospholipid antibodies. Lupus, 5, 1996, C o n l e y, C. L. et R. C. Hartmann. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus. J. Lab. Clin. Invest, 31, 1952, M a c k w o r t h - Y o u n g, C. et al. High incidence of anticardiolipin antibodies in relatives of patients with systemic lupus erythematosus. J. Rheumatol., 14, 1987, M o l t a, C. et al. Childhood-onset systemic lupus erythematosus: antiphospholipid antibodies in 37 patients and their first-degree relatives. Pediatrics, 92, 1993, C e r v e r a, R. et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum., 46, 2002, D e G r o o t, P. G. et R. H. Derksen. Pathophysiology of the antiphospholipid syndrome. J. Thromb. Haemost., 3, 2005, F e i n s t e i n, D. I. et S. I. Rapaport. Acquired inhibitors of blood coagulation. Prog. Hemost. Thromb., 1, 1972, H a r r i s, E. N. et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet, 1983, A r n e t t, F. C. et al. Associations of anti-b2-glycoprotein I autoantibodies with HLA class II alleles in three ethnic groups. Arthritis Rheum., 42, 1999, A r n e t t, F. C. et al. Molecular analysis of major histocompatibility complex alleles associated with the lupus anticoagulant. J. Clin. Invest., 87, 1991, H u g h e s, G. R. V. Thrombosis, abortion, cerebral disease, and the lupus anticoagulant. Br. Med. J., 287, 1983, H u g h e s, G. R. V. The antiphospholipid syndrome: ten years on. Lancet, 342, 1993, H u g h e s, G. R. V. Hughes' syndrome: the antiphospholipid syndrome. A historical view. Lupus, 7, 1998, S R u i z - A r g u e l l e s, G. J. et al. The G20210A polymorphism in the 3'-untranslated region of the prothrombin gene in Mexican mestizo patients with primary antiphospholipid syndrome. Clin. Appl. Thromb. Hemost., 5, 1999, Hughes G. Hughes syndrome. The antiphospholipid syndrome a clinical overview. Clin. Rev. Allergy Immunol., 32, 2007, H a s e r i c k, J. R. et R. Long. Systemic lupus erythematosus preceded by falsepositive serologic test for syphilis: presentation of five cases. Ann. Intern. Med., 37, 1952, B e a u m o n t, J. L. Syndrome hemorrhagique acquis du a un anticoagulant circulant. Sang, 25, 1954, G r a n a d o s, J. et al. The role of HLA-DR alleles and complotypes through the ethnic barrier in systemic lupus erythematosus in Mexicans. Lupus, 5, 1996, M a c k i e, I. J., C. B. Colaco et S. J. Machin. Familial lupus anticoagulants. Br. J. Haematol., 67, 1987, P a b l o s, J. L. et al. Risk of thrombosis in patients with antiphospholipid antibodies and factor V Leiden mutation. J. Rheumatol., 26, 1999, M a y, K. P. et al. Different manifestations of the antiphospholipid antibody syndrome in a family with systemic lupus erythematosus. Arthritis Rheum., 36, 1993, L o c k s h i n, M. et al. Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report. Lupus, 12, 2003, L o p e z - P e d r e r a, C. et al. Proteomic analysis in monocytes of antiphospholipid syndrome patients: Deregulation of proteins related to the development of thrombosis. Arthritis Rheum., 58, 2008, M o n t i e l - M a n z a n o, G. et al. In vivo eff ects of an inhibitor of nuclear factor-kappa B on thrombogenic properties of antiphospholipid antibodies. Ann. N. Y. Acad. Sci., 1108, 2007, P a n g b o r n, M. C. A new serologically active phospholipid from beef heart. Proc. Soc. Exp. Biol. Med., 48, 1941, M e i s, P. J. et al. For the Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. The preterm prediction study: risk factors for indicated preterm births. Am. J. Obstet. Gynecol., 178, 1998, M i y a k i s, S. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J. Thromb. Haemost., 4, 2006, C a m p s, M. T. et al. Association between HLA class II antigens and primary antiphospholipid syndrome from the south of Spain. Lupus, 4, 1995, S a v i, M. et al. HLA-DR antigens and anticardiolipin antibodies in northern Italian systemic lupus erythematosus. Arthritis Rheum., 31, 1988, B e r t o l a c c i n i, M. L. et al. Prothrombin mutation is not associated with thrombosis in patients with antiphospholipid syndrome. Thromb. Haemost., 80, 1998, M u l l a, M. J. et al. Antiphospholipid antibodies induce a pro-infl ammatory response in fi rst trimester trophoblast via the TLR4/MyD88 pathway. Am. J. Reprod. Immunol., 62, 2009, G o e l, N. et al. Familial antiphospholipid antibody syndrome: criteria for disease and evidence for autosomal dominant inheritance. Arthritis Rheum., 42, 1999, L e w i s, N. M. et al. An evaluation of an angiotensinconverting enzyme gene polymorphism and the risk of arterial thrombosis in patients with the antiphospholipid syndrome. Arthritis Rheum., 43, 2000, D a g e n a i s, P. et al. A family study of the antiphospholipid syndrome associated with other autoimmune diseases. J. Rheumatol., 19, 1992,
8 33,. IX,. 4/ P i e r a n g e l i, S. S. et al. Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms. Semin. Thromb. Hemost., 34, 2008, F o r d, P. M. et al. Premature stroke in a family with lupus anticoagulant and antiphospholipid antibodies. Stroke, 21, 1990, A m e s, P. R. et al. Thrombophilic genotypes in subjects with idiopathic antiphospholipid antibodies--prevalence and significance. Thromb. Haemost., 79, 1998, A s h e r s o n, R. A., R Cervera et J. Font. Multiorgan thrombotic disorders in systemic lupus erythematosus: a common link? Lupus, 1, 1992, S i m a n t o v, R. et al. Factor V Leiden increases the risk of thrombosis in patients with antiphospholipid antibodies. Thromb. Res., 84, 1996, B e n t o l i l a, S. et al. Lack of association between thrombosis in primary antiphospholipid syndrome and the recently described thrombophilic 3'-untranslated prothrombin gene polymorphism. Thromb. Haemost., 78, 1997, G o l d b e r g, S. N., A. M. Conti-Kelly et T. P. Greco. A family study of anticardiolipin antibodies and associated clinical conditions. Am. J. Med., 99, 1995, Y a s u d a, S. et al. Gene polymorphisms of tissue plasminogen activator and plasminogen activator inhibitor-1 in patients with antiphospholipid antibodies. J. Rheumatol., 29, 2002, T e k t o n i d o u, M. G. et al. Antiphospholipid syndrome nephropathy in patients with systemic lupus erythematosus and antiphospholipid antibodies: prevalence, clinical associations and long-term outcome. Artritis Rheum., 50, 2004, 8, V e g a - O s t e r t a g, M. et al. Involvement of p38 MAPK in the up-regulation of tissue factor on endothelial cells by antiphospholipid antibodies. Arhritis Rheum., 52, 2005, 5, W i l s o n, W. A. et al. Familial anticardiolipin antibodies and C4 deficiency that coexist with MHC DQB1 risk factors. J. Rheumatol., 22, 1995, : -.. " " Address for correspondence: N. Stoilov, M. D. Clinic of Rheumatology Medical University 13, Urvitch Str. Bg 1612 Sofia
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